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BAPTA-AM, an intracellular calcium chelator, inhibits RANKL-induced bone marrow macrophages differentiation through MEK/ERK, p38 MAPK and Akt, but not JNK pathways.
MedLine Citation:
PMID:  20667748     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
To examine the roles of intracellular calcium in RANKL-induced bone marrow macrophages (BMMs) differentiation, the effects of intracellular calcium chelator BAPTA-AM on RANKL-induced BMMs differentiation, and the activation of its relating signal proteins (MAPKs, and the PI3K/Akt) were studied. BMMs were cultured with various concentrations of BAPTA-AM in the presence of M-CSF (25 ng/ml) and RANKL (25 ng/ml) for 7 days, osteoclastogenic ability, cytosolic free Ca(2+) concentration, osteoclast survival and the expression of phosphorylated ERK1/2, SAPK/JNK, Akt and p38 MAPK were measured by TRAP staining, spectrofluorometer and Western blotting. BAPTA-AM inhibited osteoclastogenesis and osteoclast survival of BMMs by RANKL induction. In osteoclasts without the pretreatment of BAPTA-AM, the increased response of [Ca(2+)](i) was observed within 15 min and the maximum was about 1.2 times that of control. This response was sustained for 30 min and returned to the control level at 1h after RANKL-inducing, and the increased response of [Ca(2+)](i) was completely abolished and sustained to at least 8h by BAPTA-AM. Although immunoblotting data revealed that RANKL could activate the phosphorylation of ERK1/2, SAPK/JNK, Akt and p38 MAPK, the expression of ERK1/2, Akt and p38 MAPK phosphorylation was inhibited by BAPTA-AM dose-dependently. These results revealed that BAPTA-AM inhibit osteoclastogenic ability of BMMs via suppressing the increase of [Ca(2+)](i) which lead to inhibit RANKL-induced the phosphorylation of ERK, Akt and p38 MAPK, but not JNK. This finding may be useful in the development of an osteoclastic inhibitor that targets intracellular signaling factors.
Authors:
Sigui Zhou; Xi Yuan; Qinghua Liu; Xiaoqi Zhang; Xuediao Pan; Linquan Zang; Lipeng Xu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-27
Journal Detail:
Title:  Cytokine     Volume:  52     ISSN:  1096-0023     ISO Abbreviation:  Cytokine     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9005353     Medline TA:  Cytokine     Country:  United States    
Other Details:
Languages:  eng     Pagination:  210-4     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Pharmacology, GuangDong Pharmaceutical University, No. 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou, China.
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